The Gene Therapy Program (GTP) at the University of Pennsylvania (UPenn) continues to provide critical technical resources and leadership to the evolving field of cell and gene therapy for genetic diseases that include CF. The NIDDK P30 Center currently entitled Molecular Therapy for Cystic Fibrosis (CF) remains the flagship of the GTP, having been in existence for the entire 20 years that the PI (James M. Wilson) has been at UPenn. For this new cycle, the original single center has been transformed into a four center consortium. The main theme of the Center [Gene Therapy Program - CF Translational Research Consortium (GTP - CFTRC)] is the progression of molecular therapies into proof-of-concept phase 1 clinical trials. The GTP - CFTRC consists of four renowned institutions with a long-standing history in basic and translational CF research: UPenn (Wilson), University of Massachusetts Medical School (Flotte), Johns Hopkins University (Cebotaru/Guggino) and the United Kingdom CF Gene Therapy Consortium (Alton). Each of these centers brings with it experience in vector development, animal models, airway gene delivery, design and support of IND-enabling studies and progression into clinical trials. The outstanding success of the Pilot and Feasibility Program since its inception in 1993 reinforced the importance of innovative research in advancing the field of CF. It also prompted the GTP - CFTRC to increase its commitment to the Pilot and Feasibility Program by proposing, in this renewal, four applications for funding. The outstanding academic environment at the four centers of the GTP - CFTRC, as well as the highly respected research faculty, will allow for the conduct of innovative research in CF through the well-documented mechanism of collaboration that remains the essence of our consortium.